Sakae Y, Takada H, Ichinose S, Nakajima M, Sakai A, Ogawa R
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Japan.
Department of Anti-Aging and Preventive Medicine, Nippon Medical School, Japan.
Biochem Biophys Rep. 2023 Jul 20;35:101514. doi: 10.1016/j.bbrep.2023.101514. eCollection 2023 Sep.
Impaired microcirculation can cause lymphatic leakage which leads to a chronic swelling in the tissues of the body. However, no successful treatment gives any protection against lymphedema due to the lack of well-revealed pathophysiology of secondary lymphedema. Binary image of laminin immunohistochemical expression revealed that distribution of laminin expression localized during surgically induced lymphedema. 67 kDa laminin receptor (67LR) mRNA expression showed a peak at during lymphedema exacerbation. Since the response of 67LR molecules may affect the prevention of inflammation and edema, here we have hypothesized that 67LR ligand of YIGSR peptide could permit reconstructive environment for amelioration of lymphedema and evaluated the effect of YIGSR in a mouse tail model of lymphedema. Indeed, intra-abdominal injections of YIGSR for the first 3 days after inducing lymphedema in the mouse tail model reduced the tail lymphedema on day 14 by 27% (P = 0.035). Histology showed that YIGSR treatment protected lymphedema impairment in epidermis and dermis, and it also inhibited the expansion of intercellular spaces and enhanced especially cell adhesion in the basement membrane as revealed by transmission electron microscopy. Interestingly, the treatment also reduced the local expression of transforming growth factor (TGF)β. Further elucidation of the mechanisms of 67LR-facilitated lymphangiogenesis contributes to find potential targets for the treatment of lymphedema.
微循环受损会导致淋巴液渗漏，进而引起身体组织的慢性肿胀。然而，由于继发性淋巴水肿的病理生理学尚未完全阐明，目前尚无成功的治疗方法能够预防淋巴水肿。层粘连蛋白免疫组化表达的二元图像显示，层粘连蛋白表达的分布在手术诱导的淋巴水肿期间定位。67 kDa层粘连蛋白受体（67LR）mRNA表达在淋巴水肿加重期间出现峰值。由于67LR分子的反应可能影响炎症和水肿的预防，因此我们推测YIGSR肽的67LR配体可以为改善淋巴水肿提供重建环境，并在小鼠尾部淋巴水肿模型中评估了YIGSR的作用。事实上，在小鼠尾部模型中诱导淋巴水肿后的前3天腹腔注射YIGSR，可使第14天的尾部淋巴水肿减轻27%（P = 0.035）。组织学显示，YIGSR治疗可保护表皮和真皮中的淋巴水肿损伤，并且如透射电子显微镜所示，它还抑制细胞间隙的扩大，尤其增强基底膜中的细胞粘附。有趣的是，该治疗还降低了转化生长因子（TGF）β的局部表达。进一步阐明67LR促进淋巴管生成的机制有助于找到治疗淋巴水肿的潜在靶点。
